Cell Culturing and Substance Production
Cells generally exist as three-dimensional aggregates in the body. However, when cells are cultured in an artificial environment, it is common to use the classical plate culture method in which the cells are cultured two-dimensionally in a manner plated as a monolayer on the bottom of the culturing vessel, or a suspension culture method in which cells are cultured while dispersed in a liquid culture solution. Cells most suited for the plate culture method are cells having relatively high adhesion, but even when such suitable cells are used, differences in the culturing environment can often result in significant changes in the properties of the cells. With suspension culture methods as well, certain cells are suitable while others are not.
With increasing demand for in vivo proteins to be used for medical purposes, such as vaccines, enzymes, hormones, antibodies, cytokines and the like, interest is becoming increasingly focused on mass production of such in vivo proteins by cell culturing. For suspended cells of E. coli and the like, research is being conducted on techniques for mass culturing in large-scale culturing tanks. Mass culturing of suspended cells using large-scale culturing tanks requires large volumes of culture solution and an agitating apparatus. Increasing focus is also being directed toward research in which substances are produced using adherent cells, as research on such cells continues to progress. In the case of adherent cells, the cells will only expand two-dimensionally when the classical plate culture method is employed, and therefore a large culturing area is necessary. In order to perform mass production of in vivo proteins, etc., a lot of researches are also being conducted on cell culture carriers and bioreactors for three-dimensional and mass cell culture.
Microcarriers, which are microparticles on which cells can adhere and grow, are being widely studied as typical cell culturing supports (PTL 3). Different types of microcarriers have been studied and developed, and many are available on the market. They are often used for production of vaccines and proteins, and widely employed as methodologies in upscalable systems. In microcarrier culturing, however, the microcarriers must be adequately stirred and diffused to avoid their aggregation, and this places a limit on the cell culture volume. Moreover, for production of a substance, for example, the procedure is methodologically complex as well, since fine particles must be separated with a fractionating filter or the like in order to separate the carrier itself. In addition, since the form of the particulate matter of a microcarrier used in microcarrier culturing is limited, it is impossible to avoid the properties that arise from its form.
Alternative methods to microcarrier culturing have been discovered, such as methods of continuous mass culturing of spheroid cells by three-dimensional culturing using methyl cellulose or gellan gum. It is indeed possible to achieve mass culturing of cells in a bioreactor using a cellulose sponge. Being a large closed system, however, there are many restrictions on its operation, such as the inability to easily contact the culturing environment.
It has been a goal to establish a novel system that is suited for convenience and automation and that allows efficient production of numerous substances in large quantities in cells.
Porous Polyimide Film
The term “polyimide” is a general term for polymers including imide bonds in the repeating unit. An “aromatic polyimide” is a polymer in which aromatic compounds are directly linked by imide bonds. An aromatic polyimide has an aromatic-aromatic conjugated structure via an imide bond, and therefore has a strong rigid molecular structure, and since the imide bonds provide powerful intermolecular force, it has very high levels of thermal, mechanical and chemical properties.
Porous polyimide films have been utilized in the prior art for filters and low permittivity films, and especially for battery-related purposes, such as fuel cell electrolyte membranes and the like. PTLs 6 to 8 describe porous polyimide films with numerous macro-voids, having excellent permeability for gases and the like, high porosity, excellent smoothness on both surfaces, relatively high strength and, despite high porosity, also excellent resistance against compression stress in the film thickness direction. All of these are porous polyimide films formed via amic acid.